Table 2.

Tissue-specific regulatory-element enrichment analyses of the GWAS loci (GWAS SNPs and SNPs in LD with the GWAS SNPs)

SNP ID	In/near gene	SNP functional role	Coding variant function by Polyphen2	Number of SNPs in LDa	p-valueb of tissue-specific regulatory element enrichment analysesc in five tissuesd
					Skeletal muscle	Smooth muscle	Fat	Brain	Blood	Gastrointestinal tract
rs2943656	IRS1	Intergenic		86	0.14	0.38	1 × 10−7	0.04	0.82	1
rs9991501	HSD17B11	Exonic missense	Benign (Arg283Gln)	1	NAe	NA	NA	NA	NA	NA
rs2287926	VCAN	Exonic missense	Possibly damaging (Gly428Asp)	5	1 × 10−7	1 × 10−7	1 × 10−7	1 × 10−7	1	0.98
rs4842924	ADAMTSL3	Intronic		87	1 × 10−7	1 × 10−7	1 × 10−7	1 × 10−7	1	0.23
rs9936385	FTO	Intronic		91	0.78	0.38	0.49	0.45	1	0.51

^aSNPs in LD: number of SNPs in LD (r ² ≥ 0.8 and MAF ≥ 1%, based on CEU samples in the 1000 Genome Project) with the lead GWAS SNP in each locus

^bMinimum p-value permutation tests: this analysis included all SNPs in LD with the GWS lead SNPs. Multiple testing correction was done by the minimum p-value permutation test. Permutation p-values <0.05 are considered as statistically significant.

^cEnhancers and promoters (regulatory elements) in 25 chromatin states (retrieved from HaploReg4 database): SNPs are located within active regulatory elements, including promoter upstream TSS, promoter downstream TSS 1, promoter downstream TSS 2, transcribed and regulatory (prom/enh), transcribed 5ʹ preferential and enh, transcribed 3ʹ preferential and enh, transcribed and weak enhancer, active enhancer 1, active enhancer 2, active enhancer flank, weak enhancer 1, weak enhancer 2, primary H3K27ac possible enhancer, poised promoter, and bivalent promoter

^dSee Supplementary Note 2.6 for description of human primary cells and tissues that were included in each tissue group

^eWe did not perform enrichment analysis on rs9991501 because rs9991501 has no other SNPs in LD to obtain overlapping regulatory elements